Plant-derived bioactives have been used for decades for a variety of ailments. However, due to poor bioavailability high doses are required to elicit response, and the high doses may be toxic or may not be translatable to human use. Curcumin and green tea polyphenols represent some of the most investigated bioactives in both pre-clinical and clinical studies. Numerous formulations including liposomal, polymeric nanoparticles, micelles and emulsions have been reported for curcumin and other plant bioactives but none have met the clinical needs due to lack of scalability, costs and/or toxicity issues.
Chemotherapeutics are generally administered intravenously because of poor oral absorption/bioavailability. However, intravenous administration can cause blood spikes which may result in severe to life-threatening toxicities Taxanes are chemotherapeutics routinely used in the treatment of a broad spectrum of cancers, including lung, breast, ovarian, pancreas and cervical cancers. As with many other chemotherapeutic drugs, taxanes exhibit poor oral bioavailability; hence, they are administered intravenously, which is accompanied by spikes in blood levels, resulting in severe toxicities. Taxanes further suffer from having a low solubility and lack of long-term stability.
Oral chemotherapy offers many advantages over intravenous administration—including flexibility of timing and location of administration, flexibility of drug exposure, reduction of the use of the healthcare resources for in-patient and ambulatory-patient care services, and a better quality of life. However, the poor gastrointestinal absorption and hepatic first-pass effect related to many of these compounds means that bolus doses are required to achieve efficacy. To overcome this obstacle, several drug delivery systems have been developed, including liposomes, gold nanoparticles, carbon nanotubes, polymeric micelles, and polymeric implants. Of these, the liposomal delivery system has advanced the most: some chemotherapeutic drugs (e.g., doxorubicin) in liposomal formulations are already being used clinically, and a few others (cisplatin, oxaliplatin, and paclitaxel) are in Phase I/II clinical trials. However, without modification, these liposome formulations suffer from short-term blood-circulation time, instability in vivo, and a lack of target selectivity. Other limitations of liposomal systems include opsonisation and pharmacokinetic changes in multiple-dosing regimens.
Efforts to overcome these limitations have presented different challenges. For example, targeted liposomal formulations using immunoliposomes have been shown to improve efficacy; however, the immunoliposomes are rapidly eliminated from cells. Polymer-based delivery systems, including polymeric micelles, offer the advantages of linking various ligands to the surface; however, cost-effective, large-scale production and the elimination of toxicity remain elusive.
Recent studies have evaluated the use of exosomes as drug carriers. Exosomes are lipid-bilayer nanovesicles (30-100 nm) which are secreted by all cell types and occur naturally in such body fluids as blood, saliva, urine, and breast milk. In theory, exosomes have a) the potential to provide an appropriate drug delivery system due to their nano-scale size; b) a capability of loading both lipophilic and hydrophilic agents; c) the capacity to stabilize drugs, even in an acidic environment; and d) the potential ability to cross the blood brain barrier. By modifying membrane proteins, exosomes can become a desirable targeted-delivery approach.
Milk collected during day 1-2 after calving, the so-called colostrum, and mature milk contain a significant amount of exosomes and have been reported to carry a pay load of miRNAs, mRNAs, proteins and DNA. Exosomes isolated from milk can serve as a carrier of small therapeutic drugs and natural products, and milk-derived exosomes loaded with drugs have demonstrated significantly higher biological activities than naked drugs. In the past decade, standardized whole colostrum powder from bovine colostrum has become available commercially. Thus, it would be beneficial if an efficient means was available to isolate exosomes from this standardized whole colostrum powder.